therapeutic vaccine plus pd-1 knockout in prostate cancer treatment

Conditions: Prostate Cancer

Summary: this study is to evaluate the safety and efficacy of a therapeutic vaccine in combination with pd-1 knockout t cells in the treatment of advanced prostate cancer.

this is a phase 1/2 clinical study investigating the safety and efficacy of a therapeutic vaccine in combination with pd-1 knockout t cells in the treatment of advanced prostate cancer. the therapeutic vaccine is a customized product involving ex vivo treatment of the patient's peripheral blood mononuclear cells with a recombinant fusion protein (pap-gm-csf) to activate the expression of the antigen that would activate the immune function to kill cancer cells. the pd-1 knockout engineered t cells are also prepared using patient's t cells in which pd-1 gene will be knocked out using crispr cas9 technology. the therapeutic vaccine and pd-1 knockout t cells will be infused back to the patient in 3 times with a 2-week interval.

Eligibility criteria:
inclusion criteria: * • histologically confirmed prostate cancer (stage iv, according to nccn clinical practice guidelines in oncology: prostate cancer, version 2.2017) * evidence of metastasis in the soft tissue and/or bone. * progressive androgen independent castrate resistant prostate cancer. * serum psa ≥ 5.0 ng/ml * estimated life expectancy ≥ 6 months. * castrate level of testosterone (\< 50 ng/dl) achieved via medical or surgical castration. * adequate hematologic, renal and liver function. exclusion criteria: * • presence of known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites. * presence of moderate to severe pain treating with opioid analgesics within 21 days prior to registration. * ecog score ≥ 2. * any other systemic therapy for prostate cancer (except for medical castration). * participation in previous study using provenge (sipuleucel-t) or similar product. * known pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography \> 50%) or spinal cord compression. * known malignancies other than prostate cancer requiring active treatment within 6 months. * a requirement for systemic immunosuppressive therapy for any reason. * a history of allergic reactions attributed to compounds of similar chemical or biologic composition to this product or granulocyte-macrophage colony-stimulating factor. * any infection requiring parenteral antibiotic therapy or causing fever (temp \> 100.5°f or \> 38.1°c) within 1 week prior to registration. * any medical intervention or other condition which, in the opinion of the principal investigator could compromise adherence with study requirements or otherwise compromise the study's objectives. * treatment with any of the following medications or interventions within 28 days of registration: systemic use of corticosteroids, external beam radiation therapy or surgery, use of non-steroidal antiandrogens dietary and herbal supplements, as well as alternative treatments that have evidence of hormonal and/or anticancer properties (e.g., prostate cancer (pc) -spes or pc-spec) and saw palmetto, megestrol acetate (megace®), diethylstilbesterol (des), or cyproterone acetate, ++ketoconazole, 5-alpha-reductase inhibitors, treatment with any other investigational product treatment with chemotherapy high dose calcitriol \[1,25(oh)2vitamin d\] (i.e., \> 0.5 mcg/day). initiation or discontinuation of bisphosphonate therapy

Keywords: prostate cancer therapeutic vaccine pd-1 knockout